This Notice of Special Interest (NOSI) highlights the urgent need for research strategies and interventions to address SARS-CoV-2 vaccine hesitancy, uptake, and implementation among populations who experience health disparities in the United States (U.S.). Research is urgently needed to understand and address misinformation, distrust, and hesitancy regarding the SARS-CoV-2 (COVID-19) vaccine among adults in the U.S. and its territories, especially among populations who are at increased risk for morbidity and mortality due to long-standing systemic health and social inequities and chronic medical conditions. ThisNOSI solicits community-engaged research to: 1) evaluate innovative interventions to facilitate vaccination uptake in clinical and community contexts; and 2) address the barriers to increasing reach, access, and uptake of vaccinations among health disparity populations. Applications for this NOSI are limited to NIH Research Centers in Minority Institution's (RCMI) currently active U54 awards, which are not in an extension at the time of application submission.